Gait & Posture 41 (2015) 780–785
Contents lists available at ScienceDirect
Gait & Posture journal homepage: www.elsevier.com/locate/gaitpost
Investigating the phenomenon of ‘‘cognitive-motor interference’’ in multiple sclerosis by means of dual-task posturography Luca Prosperini a,*, Letizia Castelli b, Giovanni Sellitto b, Francesca De Luca a, Laura De Giglio a, Flavia Gurreri c, Carlo Pozzilli a a b c
Dept of Neurology and Psychiatry, Sapienza University, Rome Physical Therapy Unit, S. Andrea Hospital, Rome Neurological Center of Latium, Rome
A R T I C L E I N F O
A B S T R A C T
Article history: Received 4 November 2014 Received in revised form 6 January 2015 Accepted 14 February 2015
Background: Two simultaneously performed tasks may compete for common brain network resources in patients with multiple sclerosis (MS), suggesting the occurrence of a cognitive-motor interference. While this phenomenon has been well described for walking and gait, data on static balance are scarce. Methods: In this cross-sectional study, 92 patients and 46 sex/age-matched healthy controls (HCs) were tested by means of static posturography under eyes opened (single-task condition) and while performing the Stroop word-colour task (dual-task condition), to estimate the dual-task cost (DTC) of standing balance. The patient group also underwent the Expanded Disability Status Scale, 25-foot walking test, 12-item MS walking scale, Modified Fatigue Impact Scale, and Symbol Digit Modalities Test. Results: Patients had larger postural sway under both single-task and dual-task conditions (p < 0.001), as well as greater DTC of standing balance (p = 0.021) than HCs. Although secondary progressive (SP) patients had larger sway in both conditions than relapsing-remitting (RR) patients (p < 0.05), these latter ones exhibited a greater DTC of postural balance (p = 0.045). Deficits in sustained attention and information processing speed, as assessed by the SDMT, were also independently associated with the magnitude of DTC of standing balance (p = 0.005). Conclusions: The phenomenon of cognitive-motor interference might be unmasked by a dual-task posturography and was associated with impaired sustained attention and information processing speed, especially in RR patients. The smaller DTC of standing balance observed in SP patients may be due to the ceiling effect of postural sway, or alternatively to the lack of postural reserve which constrained the more disabled patients to prioritize the balance over the cognitive task. ß 2015 Elsevier B.V. All rights reserved.
Keywords: Multiple sclerosis Balance Cognition Dual-task cost Posturography Attention
1. Introduction Some evidence supports the notion of a decrement in walking and balance skills when performed in conjunction with a simultaneous cognitive task, indicating the existence of a cognitive-motor interference phenomenon, especially in elderly people and in subjects affected by neurological diseases [1]. Cognitive-motor interference can be specifically investigated by means of dual-tasking paradigm, i.e. a study design aimed at assessing the attentional resources allocated to a task of interest
* Corresponding author at: Multiple Sclerosis Centre, S. Andrea Hospital, Dept. of Neurology and Psychiatry, Sapienza University, Viale dell’Universita`, 30-00185 Rome, Italy. Tel.: +39 06 49914716; fax: +39 06 33775900. E-mail address: [email protected] (L. Prosperini). http://dx.doi.org/10.1016/j.gaitpost.2015.02.002 0966-6362/ß 2015 Elsevier B.V. All rights reserved.
[1,2]. The dual-task cost (DTC), calculated as change from singleto dual-task condition, is considered a measure of cognitivemotor interference [2]. Multiple sclerosis (MS) is a central nervous system disease associated with inflammation, demyelination, and axonal damage, that may affect the higher-level cognitive processing, timely integration of multi-modal sensorial information and motor output. As a consequence, patients with MS exhibit deficits in gait and balance, as well as cognitive dysfunction even at the earliest stage of the disease, with varying degrees of overlap [3,4]. Specifically, the cognitive functions most often involved are information processing speed, sustained attention, and some aspects of executive functions [4]. Deficits in attention and executive function processes have been also independently associated not only with deteriorated
L. Prosperini et al. / Gait & Posture 41 (2015) 780–785
walking performance, but also with postural instability and future falls in MS [5], suggesting that motor skills, balance and cognition are processed by neural pathways involving shared networks [6–8]. According to a recent topical review, the DTC of walking is associated with slower short-distance speed, worse gait performance, and increased risk of falls in patients with MS, regardless of the cognitive task demand [9]. By contrast, only few studies have investigated the impact of dual tasking on postural balance of patients with MS so far, providing less consistent findings [10–15]. Some of these studies do not report any estimate of DTC [10–12,14], lack of a healthy control group [13,15], or provide conflicting results about factors which may potentially affect the dual-task performance, including fatigue and disability level [13–15]. In this context, static posturography provides objective, linear and reliable measurements of standing balance, and also exhibits more sensitivity than common clinical scales in identifying patients at risk of falls [16,17]. Moreover, it may reveal subclinical balance disorders undetectable by a routinely clinical assessment, even in patients not complaining about balance impairment, or in minimally impaired patients [18–20]. For these reasons, DTCbased measures of balance may represent a promising tool for detecting subtle disability, disease progression and intervention effectiveness, since they may reflect the real-life performance better than assessing motor and cognitive abilities separately [9]. Therefore, in this study we aimed at investigating whether: (i) a dual-task paradigm, applied to static posturography, may detect the cognitive-motor interference phenomenon in MS; (ii) the DTC of standing balance differs among MS phenotypes; (iii) there are demographic and clinical factors associated with DTC of standing balance.
781
studies; an informed consent was obtained from each participant before any study procedure. 2.2. Study procedures
2. Methods
Patients with MS underwent a complete neurological examination including the Expanded Disability Status Scale (EDSS) scoring [24], 25-foot walking test (25-FWT) [25], 12-item MS walking scale (MSWS-12) [26], Modified Fatigue Impact Scale (MFIS) [27], and Symbol Digit Modalities Test (SDMT) [28]. The EDSS is the most common method of quantifying disability in MS people, by evaluating eight different functional systems (pyramidal, cerebellar, brainstem, sensory, bowel/bladder, visual, cerebral, other); it ranges from 0 to 10, in 0.5 unit increments that represent higher levels of disability [24]. The 25-FWT is a stopwatch measurement of time (seconds) to walk a 25-foot (7.6 m) distance; it has shown good reliability and validity, and represents the most characterized measure of walking speed in MS setting [25]. The MSWS-12 is a patient-rated 12-item questionnaire that assesses limitations to the patient’s walking ability because of MS in the past two weeks; higher scores indicate greater impact [26]. The MFIS is a 21-item self-administered questionnaire based on items derived from interviews with patients with MS concerning how fatigue impacts their lives; it comprises three subscales (physical, cognitive, and psychosocial functioning); higher scores indicate greater fatigue [27]. The SDMT is a measure of sustained attention and information processing speed that has been reported as an easy and quick tool to detect cognitive dysfunction in everyday clinical setting, yielding a sensitivity of 82%, specificity of 60%, and overall accuracy of 72% [28]; all SDMT scores were corrected by educational level as recommended elsewhere [29].
2.1. Participants
2.3. Outcome measures
Patients diagnosed as affected by MS according to 2010 revised McDonald criteria [21] and regularly attending the MS centre of S. Andrea Hospital in Rome were screened for eligibility from November 2013 to May 2014 by the agreement of a psychologist and a neurologist. Inclusion criteria were: age between 18 and 55 years (inclusive); relapsing-remitting (RR) or secondary progressive (SP) phenotype; ability to stand upright for at least 180 s without any support; ability to understand and comply with study requirements; voluntarily provide a valid informed consent before any study procedure. Exclusion criteria were: disease exacerbation in the previous three months; primary progressive phenotype; current use of oral/systemic corticosteroids; initiation of disease-modifying or symptomatic treatments, or any medication change occurring over the previous month; severely blurred vision. In order to avoid the possibility that mood disorders could affect the dual-task paradigm, we also excluded patients with clinically relevant depression, defined as Beck Depression Inventory-II (BDI-II) score more than 12 [22]. Patients with severe cognitive impairment, defined as Mini Mental State Examination (MMSE) score less than 25 [23], were also excluded because potentially not able to accomplish with study procedures. Gender/age/education level-matched healthy controls (HCs) were recruited in a 1:2 ratio among the personnel (stretcher bearers, technicians, students, residents, nurses, physiotherapists, doctors) operating at the S. Andrea Hospital. The present study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The ethical committee board of Sapienza University provided exemption of approval for non-interventional
Each participant was tested by means of static posturography under single-task and dual-task conditions, using a laboratorygrade force platform (ProKin PK-254P, Tecnobody, Bergamo, Italy; http://www.tecnobody.it) according to standardized procedures [17]. Participants were instructed to maintain their balance for 30 s as steady as possible under eyes opened (single-task condition) and while performing the Stroop word-colour task (dual-task condition) presented on a printout located at a 2-meter from the force platform, as described elsewhere [11]. During the dual-task condition, participants were asked to prioritize the cognitive task and had to restart from the first coloured word in case of error; the number of errors at Stroop test was also recorded. The instant position of the centre of pressure (COP) on the ground was used to calculate the postural sway, i.e. the sum of displacements (millimeters) on the force-measuring platform under eyes opened (single-task condition, COP pathEO) and concurrent cognitive interference (dual-task condition, COP pathStroop); larger sway indicates worse standing balance. When compared with other static standing balance measurements, such as ellipse area, antero-posterior or medio-lateral velocity, the COP path exhibits the best test-retest reliability [17]. According to literature data, the DTC was calculated as DTC = (dual-task single-task)/single-task 100 [2], that is DTC = (COP pathStroop COP pathEO)/COP pathEO. 2.4. Statistical analysis Statistical inferences were carried out by using non-parametric tests, since an exploratory analysis of data distribution (ShapiroWilk test) revealed that the afore defined outcome measures were
782
L. Prosperini et al. / Gait & Posture 41 (2015) 780–785
not normally distributed. Where the application of non-parametric test was not possible, data were properly transformed. Differences between patients and HCs were tested using the Mann-Whitney U test and Chi-square test with Yate’s correction, as appropriate. A two-way analysis of the variance (ANOVA) with a 2 3 design was carried out to evaluate the effect of condition (single-task versus dual-task) as within-groups factor, and subject subgroups (RR, SP, HCs) as between-groups factor on log10 [COP path]. Differences in cube-root [DTC] between the same subgroups of (RR, SP and HCs) were also analyzed by means of one-way ANOVA, with least significant difference (LSD) post-hoc comparisons; effect sizes were also expressed as eta-squared. Spearman rank correlation coefficients were carried out to test relationships between outcome measures and other demographic and clinical variables, including age, height, weight, body mass index (BMI), educational level, disease duration, EDSS score, walking speed, MSWS-12, MFIS and its subscales, corrected SDMT, and number of errors at Stroop test (i.e. while performing the static posturography assessment in dual-task condition). Lastly, stepwise linear regression models were built to identify independent variables (among those afore mentioned) significantly associated with COP pathEO [log10], COP pathStroop [log10], and DTC [cube-root]; in each subsequent step, the regression equation comprised those factors reaching specific thresholds of F- and pvalues (for inclusion: F 1 and p 0.05; for exclusion: F < 1 and p > 0.10). P-values less than 0.05 in either direction were considered as significant. Statistical analyses were carried out using the Statistical Package for Social Sciences, version 16.0 (IBM SPSS, Chicago, IL, USA).
3. Results 3.1. Participants Out of 106 screened patients, 12 were excluded for the following reasons: 10 patients did not meet inclusion criteria (BDI-II score >12, n = 8; MMSE score 0.4) (Table 1). As expected, HCs (n = 46) performed significantly better than patients with MS (n = 92) in terms of postural sway in either singletask [COP pathEO: 198 (70) versus 298 (141) mm, p < 0.001] and dual-task condition [COP pathStroop: 231 (79) versus 406 (199) mm, p < 0.001]. Dual-task posturography was able to detect the cognitive motor-interference in patients contrasted to HCs, as revealed by the significant difference in the median DTC of standing balance (31% versus 22%, p = 0.021) with a moderate effect size (eta-squared = 0.06). The number of errors at Stroop test was higher in patients than in HCs (median 0, range 0–7, and median 0, range 0–2, respectively; p = 0.042). Interestingly, we also found a negative DTC of standing balance in 14 (15.2%) patients and 12 (26.1%) HCs (p = 0.1), suggesting that in these subjects the concurrent cognitive task exerted a stabilizing effect on balance. Patients with negative DTC (n = 14) had a higher mean corrected SDMT scores than those with positive DTC (n = 78) of standing balance (44.1 versus 37.7, p = 0.019) but there were no
Table 1 Demographic and clinical characteristics of study participants.
Gender, F:M Age (years) Height (m) Weight (kg) BMI (kg/m2) Educational level (years) COP pathEO (mm) COP pathStroop (mm) DTC (%), median [IQR] Phenotype, RR:SP Disease duration (years) EDSS score, median [range] Walking speed (m/s) MSWS-12 score MFIS total score Physical subscore Cognitive subscore Psychological subscore SDMT corrected score
Patients with MS, n = 92
Healthy controls, n = 46
60:32 39.2 (10.1) 1.68 (0.08) 64.2 (12.4) 22.9 (4.0) 13.6 (3.7) 298 (140) 405 (199) 31 [6–68] 67:25 11.8 (8.1) 2.5 [1.0–6.0] 1.27 (0.39) 42.8 (24.5) 28.9 (20.4) 15.3 (10.6) 10.8 (9.6) 2.7 (2.3) 38.7 (11.2)
30:16 39.3 (9.8) 1.67 (0.09) 66.6 (11.9) 23.6 (3.9) 13.8 (3.3) 198 (70)* 231 (79)* 23 [0–39]* N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
All values are mean (standard deviation) unless indicated otherwise. F: females; M: males; BMI: body mass index; COP: center of pressure; EO: eyes opened; DTC: dual-task cost; IQR: interquartile range; RR: relapsing-remitting; SP: secondary progressive; EDSS: Expanded Disability Status Scale; MSWS-12: 12-item Multiple Sclerosis Waking Scale; MFIS: Modified Fatigue Impact Scale; SDMT: Symbol Digit Modalities Test; N/A: not applicable. * p < 0.05.
other significant between-group differences (p > 0.1; see supplemental material for further details). 3.2. Effect of dual-tasking on different phenotypes As expected, patients with SP phenotype (n = 25) were older and more disabled, had a longer disease duration, worse postural balance in single-task and dual-task condition, slower walking speed, lower scores on MSWS-12, and were more cognitively impaired at SDMT than RR ones (n = 67) (p0.001, see supplemental material for further details). By contrast, the level of fatigue assessed with MFIS and its subscales did not differ between MS phenotypes (p > 0.3). The two-way ANOVA, being the assumption of sphericity satisfied, showed significant effects of condition (F1,135 = 67.684, p < 0.001; eta-squared = 0.31), subgroups (F2,135 = 31.681, p < 0.001; eta-squared = 0.32) and condition by group interaction (F2,135 = 5.658, p = 0.004; eta-squared: 0.05) on the COP path [log10] (see also Fig. 1). There was a significant between-group difference in DTC as determined by one-way ANOVA (F2,135 = 4.271, p = 0.015; etasquared: 0.06); LSD post-hoc test revealed that the DTC [cube-root] of standing balance was greater in RR than either HCs and SP (p = 0.012—eta-squared = 0.12, and p = 0.045—eta-squared = 0.06, respectively), while any significant difference was found between SP and HCs (p = 0.583). Notably, SP group committed a slightly greater number of errors at Stroop test than RR group (p = 0.07).
3.3. Determinants of dual-task cost of balance The Spearman’s correlations (see also Table 2) revealed that postural balance in either single-task and dual-task condition was related with MS duration, EDSS score, walking speed, MSWS-12 and corrected SDMT score (p < 0.05). Fair relationships were also found between COP pathStroop and age (p = 0.005), and between DTC of standing balance and corrected SDMT (p = 0.021). The number of errors at Stroop test did not correlate neither with posturographic measures, nor with DTC or SDMT (p > 0.05).
L. Prosperini et al. / Gait & Posture 41 (2015) 780–785
783
accounted for about 40% of the explained variability in this measure; the regression equation was: COP pathStroop [log10] = 2.551 + 0.091 (EDSS score) 0.005 (corrected SDMT score). The DTC of standing balance was associated with phenotype and corrected SDMT score; these two variables accounted for about 30% of the explained variability in this measure; the regression equation was: COP pathStroop [log10] = 5.908 1.472 (1 if SP, 0 if RR) 0.061 (corrected SDMT score). 4. Discussion
Fig. 1. Postural sway, expressed as mean centre of pressure (COP) path [log10] with relative 95% confidence intervals, for each group (relapsing-remitting multiple sclerosis, secondary-progressive multiple sclerosis and healthy controls) and condition (single-task: eyes opened, and dual-task: while performing the Stroop test).
In HC group a significant relationship was observed between COP pathEO and height (rho = 0.352, p = 0.018). Interestingly, we also found a significant relationship between DTC of standing balance and educational level (rho = 0.341, p = 0.019). Findings from multivariable linear regression analyses with outcome measures as dependent variables are shown in Table 3. Postural balance in single-task condition was associated with EDSS score; this variable accounted for about 37% of the explained variability in this measure; the regression equation was: COP pathEO [log10] = 2.396 + 0.076 (EDSS score). Postural balance in dual-task condition was associated with EDSS score and corrected SDMT score; these two variables Table 2 Non-parametric correlation coefficients, with their relative level of significance, in patients with MS (n = 92). COP pathEO
COP pathStroop
DTC
Age
rho p
0.194 0.063
0.292 0.005
0.134 0.202
Height
rho p
0.068 0.529
0.034 0.750
0.022 0.834
Weight
rho p
0.154 0.149
0.095 0.368
0.029 0.784
BMI
rho p
0.127 0.226
0.048 0.647
0.071 0.503
Educational level
rho p
0.201 0.054
0.192 0.067
0.040 0.706
Disease duration
rho p
0.291 0.005
0.391
Contents lists available at ScienceDirect
Gait & Posture journal homepage: www.elsevier.com/locate/gaitpost
Investigating the phenomenon of ‘‘cognitive-motor interference’’ in multiple sclerosis by means of dual-task posturography Luca Prosperini a,*, Letizia Castelli b, Giovanni Sellitto b, Francesca De Luca a, Laura De Giglio a, Flavia Gurreri c, Carlo Pozzilli a a b c
Dept of Neurology and Psychiatry, Sapienza University, Rome Physical Therapy Unit, S. Andrea Hospital, Rome Neurological Center of Latium, Rome
A R T I C L E I N F O
A B S T R A C T
Article history: Received 4 November 2014 Received in revised form 6 January 2015 Accepted 14 February 2015
Background: Two simultaneously performed tasks may compete for common brain network resources in patients with multiple sclerosis (MS), suggesting the occurrence of a cognitive-motor interference. While this phenomenon has been well described for walking and gait, data on static balance are scarce. Methods: In this cross-sectional study, 92 patients and 46 sex/age-matched healthy controls (HCs) were tested by means of static posturography under eyes opened (single-task condition) and while performing the Stroop word-colour task (dual-task condition), to estimate the dual-task cost (DTC) of standing balance. The patient group also underwent the Expanded Disability Status Scale, 25-foot walking test, 12-item MS walking scale, Modified Fatigue Impact Scale, and Symbol Digit Modalities Test. Results: Patients had larger postural sway under both single-task and dual-task conditions (p < 0.001), as well as greater DTC of standing balance (p = 0.021) than HCs. Although secondary progressive (SP) patients had larger sway in both conditions than relapsing-remitting (RR) patients (p < 0.05), these latter ones exhibited a greater DTC of postural balance (p = 0.045). Deficits in sustained attention and information processing speed, as assessed by the SDMT, were also independently associated with the magnitude of DTC of standing balance (p = 0.005). Conclusions: The phenomenon of cognitive-motor interference might be unmasked by a dual-task posturography and was associated with impaired sustained attention and information processing speed, especially in RR patients. The smaller DTC of standing balance observed in SP patients may be due to the ceiling effect of postural sway, or alternatively to the lack of postural reserve which constrained the more disabled patients to prioritize the balance over the cognitive task. ß 2015 Elsevier B.V. All rights reserved.
Keywords: Multiple sclerosis Balance Cognition Dual-task cost Posturography Attention
1. Introduction Some evidence supports the notion of a decrement in walking and balance skills when performed in conjunction with a simultaneous cognitive task, indicating the existence of a cognitive-motor interference phenomenon, especially in elderly people and in subjects affected by neurological diseases [1]. Cognitive-motor interference can be specifically investigated by means of dual-tasking paradigm, i.e. a study design aimed at assessing the attentional resources allocated to a task of interest
* Corresponding author at: Multiple Sclerosis Centre, S. Andrea Hospital, Dept. of Neurology and Psychiatry, Sapienza University, Viale dell’Universita`, 30-00185 Rome, Italy. Tel.: +39 06 49914716; fax: +39 06 33775900. E-mail address: [email protected] (L. Prosperini). http://dx.doi.org/10.1016/j.gaitpost.2015.02.002 0966-6362/ß 2015 Elsevier B.V. All rights reserved.
[1,2]. The dual-task cost (DTC), calculated as change from singleto dual-task condition, is considered a measure of cognitivemotor interference [2]. Multiple sclerosis (MS) is a central nervous system disease associated with inflammation, demyelination, and axonal damage, that may affect the higher-level cognitive processing, timely integration of multi-modal sensorial information and motor output. As a consequence, patients with MS exhibit deficits in gait and balance, as well as cognitive dysfunction even at the earliest stage of the disease, with varying degrees of overlap [3,4]. Specifically, the cognitive functions most often involved are information processing speed, sustained attention, and some aspects of executive functions [4]. Deficits in attention and executive function processes have been also independently associated not only with deteriorated
L. Prosperini et al. / Gait & Posture 41 (2015) 780–785
walking performance, but also with postural instability and future falls in MS [5], suggesting that motor skills, balance and cognition are processed by neural pathways involving shared networks [6–8]. According to a recent topical review, the DTC of walking is associated with slower short-distance speed, worse gait performance, and increased risk of falls in patients with MS, regardless of the cognitive task demand [9]. By contrast, only few studies have investigated the impact of dual tasking on postural balance of patients with MS so far, providing less consistent findings [10–15]. Some of these studies do not report any estimate of DTC [10–12,14], lack of a healthy control group [13,15], or provide conflicting results about factors which may potentially affect the dual-task performance, including fatigue and disability level [13–15]. In this context, static posturography provides objective, linear and reliable measurements of standing balance, and also exhibits more sensitivity than common clinical scales in identifying patients at risk of falls [16,17]. Moreover, it may reveal subclinical balance disorders undetectable by a routinely clinical assessment, even in patients not complaining about balance impairment, or in minimally impaired patients [18–20]. For these reasons, DTCbased measures of balance may represent a promising tool for detecting subtle disability, disease progression and intervention effectiveness, since they may reflect the real-life performance better than assessing motor and cognitive abilities separately [9]. Therefore, in this study we aimed at investigating whether: (i) a dual-task paradigm, applied to static posturography, may detect the cognitive-motor interference phenomenon in MS; (ii) the DTC of standing balance differs among MS phenotypes; (iii) there are demographic and clinical factors associated with DTC of standing balance.
781
studies; an informed consent was obtained from each participant before any study procedure. 2.2. Study procedures
2. Methods
Patients with MS underwent a complete neurological examination including the Expanded Disability Status Scale (EDSS) scoring [24], 25-foot walking test (25-FWT) [25], 12-item MS walking scale (MSWS-12) [26], Modified Fatigue Impact Scale (MFIS) [27], and Symbol Digit Modalities Test (SDMT) [28]. The EDSS is the most common method of quantifying disability in MS people, by evaluating eight different functional systems (pyramidal, cerebellar, brainstem, sensory, bowel/bladder, visual, cerebral, other); it ranges from 0 to 10, in 0.5 unit increments that represent higher levels of disability [24]. The 25-FWT is a stopwatch measurement of time (seconds) to walk a 25-foot (7.6 m) distance; it has shown good reliability and validity, and represents the most characterized measure of walking speed in MS setting [25]. The MSWS-12 is a patient-rated 12-item questionnaire that assesses limitations to the patient’s walking ability because of MS in the past two weeks; higher scores indicate greater impact [26]. The MFIS is a 21-item self-administered questionnaire based on items derived from interviews with patients with MS concerning how fatigue impacts their lives; it comprises three subscales (physical, cognitive, and psychosocial functioning); higher scores indicate greater fatigue [27]. The SDMT is a measure of sustained attention and information processing speed that has been reported as an easy and quick tool to detect cognitive dysfunction in everyday clinical setting, yielding a sensitivity of 82%, specificity of 60%, and overall accuracy of 72% [28]; all SDMT scores were corrected by educational level as recommended elsewhere [29].
2.1. Participants
2.3. Outcome measures
Patients diagnosed as affected by MS according to 2010 revised McDonald criteria [21] and regularly attending the MS centre of S. Andrea Hospital in Rome were screened for eligibility from November 2013 to May 2014 by the agreement of a psychologist and a neurologist. Inclusion criteria were: age between 18 and 55 years (inclusive); relapsing-remitting (RR) or secondary progressive (SP) phenotype; ability to stand upright for at least 180 s without any support; ability to understand and comply with study requirements; voluntarily provide a valid informed consent before any study procedure. Exclusion criteria were: disease exacerbation in the previous three months; primary progressive phenotype; current use of oral/systemic corticosteroids; initiation of disease-modifying or symptomatic treatments, or any medication change occurring over the previous month; severely blurred vision. In order to avoid the possibility that mood disorders could affect the dual-task paradigm, we also excluded patients with clinically relevant depression, defined as Beck Depression Inventory-II (BDI-II) score more than 12 [22]. Patients with severe cognitive impairment, defined as Mini Mental State Examination (MMSE) score less than 25 [23], were also excluded because potentially not able to accomplish with study procedures. Gender/age/education level-matched healthy controls (HCs) were recruited in a 1:2 ratio among the personnel (stretcher bearers, technicians, students, residents, nurses, physiotherapists, doctors) operating at the S. Andrea Hospital. The present study was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. The ethical committee board of Sapienza University provided exemption of approval for non-interventional
Each participant was tested by means of static posturography under single-task and dual-task conditions, using a laboratorygrade force platform (ProKin PK-254P, Tecnobody, Bergamo, Italy; http://www.tecnobody.it) according to standardized procedures [17]. Participants were instructed to maintain their balance for 30 s as steady as possible under eyes opened (single-task condition) and while performing the Stroop word-colour task (dual-task condition) presented on a printout located at a 2-meter from the force platform, as described elsewhere [11]. During the dual-task condition, participants were asked to prioritize the cognitive task and had to restart from the first coloured word in case of error; the number of errors at Stroop test was also recorded. The instant position of the centre of pressure (COP) on the ground was used to calculate the postural sway, i.e. the sum of displacements (millimeters) on the force-measuring platform under eyes opened (single-task condition, COP pathEO) and concurrent cognitive interference (dual-task condition, COP pathStroop); larger sway indicates worse standing balance. When compared with other static standing balance measurements, such as ellipse area, antero-posterior or medio-lateral velocity, the COP path exhibits the best test-retest reliability [17]. According to literature data, the DTC was calculated as DTC = (dual-task single-task)/single-task 100 [2], that is DTC = (COP pathStroop COP pathEO)/COP pathEO. 2.4. Statistical analysis Statistical inferences were carried out by using non-parametric tests, since an exploratory analysis of data distribution (ShapiroWilk test) revealed that the afore defined outcome measures were
782
L. Prosperini et al. / Gait & Posture 41 (2015) 780–785
not normally distributed. Where the application of non-parametric test was not possible, data were properly transformed. Differences between patients and HCs were tested using the Mann-Whitney U test and Chi-square test with Yate’s correction, as appropriate. A two-way analysis of the variance (ANOVA) with a 2 3 design was carried out to evaluate the effect of condition (single-task versus dual-task) as within-groups factor, and subject subgroups (RR, SP, HCs) as between-groups factor on log10 [COP path]. Differences in cube-root [DTC] between the same subgroups of (RR, SP and HCs) were also analyzed by means of one-way ANOVA, with least significant difference (LSD) post-hoc comparisons; effect sizes were also expressed as eta-squared. Spearman rank correlation coefficients were carried out to test relationships between outcome measures and other demographic and clinical variables, including age, height, weight, body mass index (BMI), educational level, disease duration, EDSS score, walking speed, MSWS-12, MFIS and its subscales, corrected SDMT, and number of errors at Stroop test (i.e. while performing the static posturography assessment in dual-task condition). Lastly, stepwise linear regression models were built to identify independent variables (among those afore mentioned) significantly associated with COP pathEO [log10], COP pathStroop [log10], and DTC [cube-root]; in each subsequent step, the regression equation comprised those factors reaching specific thresholds of F- and pvalues (for inclusion: F 1 and p 0.05; for exclusion: F < 1 and p > 0.10). P-values less than 0.05 in either direction were considered as significant. Statistical analyses were carried out using the Statistical Package for Social Sciences, version 16.0 (IBM SPSS, Chicago, IL, USA).
3. Results 3.1. Participants Out of 106 screened patients, 12 were excluded for the following reasons: 10 patients did not meet inclusion criteria (BDI-II score >12, n = 8; MMSE score 0.4) (Table 1). As expected, HCs (n = 46) performed significantly better than patients with MS (n = 92) in terms of postural sway in either singletask [COP pathEO: 198 (70) versus 298 (141) mm, p < 0.001] and dual-task condition [COP pathStroop: 231 (79) versus 406 (199) mm, p < 0.001]. Dual-task posturography was able to detect the cognitive motor-interference in patients contrasted to HCs, as revealed by the significant difference in the median DTC of standing balance (31% versus 22%, p = 0.021) with a moderate effect size (eta-squared = 0.06). The number of errors at Stroop test was higher in patients than in HCs (median 0, range 0–7, and median 0, range 0–2, respectively; p = 0.042). Interestingly, we also found a negative DTC of standing balance in 14 (15.2%) patients and 12 (26.1%) HCs (p = 0.1), suggesting that in these subjects the concurrent cognitive task exerted a stabilizing effect on balance. Patients with negative DTC (n = 14) had a higher mean corrected SDMT scores than those with positive DTC (n = 78) of standing balance (44.1 versus 37.7, p = 0.019) but there were no
Table 1 Demographic and clinical characteristics of study participants.
Gender, F:M Age (years) Height (m) Weight (kg) BMI (kg/m2) Educational level (years) COP pathEO (mm) COP pathStroop (mm) DTC (%), median [IQR] Phenotype, RR:SP Disease duration (years) EDSS score, median [range] Walking speed (m/s) MSWS-12 score MFIS total score Physical subscore Cognitive subscore Psychological subscore SDMT corrected score
Patients with MS, n = 92
Healthy controls, n = 46
60:32 39.2 (10.1) 1.68 (0.08) 64.2 (12.4) 22.9 (4.0) 13.6 (3.7) 298 (140) 405 (199) 31 [6–68] 67:25 11.8 (8.1) 2.5 [1.0–6.0] 1.27 (0.39) 42.8 (24.5) 28.9 (20.4) 15.3 (10.6) 10.8 (9.6) 2.7 (2.3) 38.7 (11.2)
30:16 39.3 (9.8) 1.67 (0.09) 66.6 (11.9) 23.6 (3.9) 13.8 (3.3) 198 (70)* 231 (79)* 23 [0–39]* N/A N/A N/A N/A N/A N/A N/A N/A N/A N/A
All values are mean (standard deviation) unless indicated otherwise. F: females; M: males; BMI: body mass index; COP: center of pressure; EO: eyes opened; DTC: dual-task cost; IQR: interquartile range; RR: relapsing-remitting; SP: secondary progressive; EDSS: Expanded Disability Status Scale; MSWS-12: 12-item Multiple Sclerosis Waking Scale; MFIS: Modified Fatigue Impact Scale; SDMT: Symbol Digit Modalities Test; N/A: not applicable. * p < 0.05.
other significant between-group differences (p > 0.1; see supplemental material for further details). 3.2. Effect of dual-tasking on different phenotypes As expected, patients with SP phenotype (n = 25) were older and more disabled, had a longer disease duration, worse postural balance in single-task and dual-task condition, slower walking speed, lower scores on MSWS-12, and were more cognitively impaired at SDMT than RR ones (n = 67) (p0.001, see supplemental material for further details). By contrast, the level of fatigue assessed with MFIS and its subscales did not differ between MS phenotypes (p > 0.3). The two-way ANOVA, being the assumption of sphericity satisfied, showed significant effects of condition (F1,135 = 67.684, p < 0.001; eta-squared = 0.31), subgroups (F2,135 = 31.681, p < 0.001; eta-squared = 0.32) and condition by group interaction (F2,135 = 5.658, p = 0.004; eta-squared: 0.05) on the COP path [log10] (see also Fig. 1). There was a significant between-group difference in DTC as determined by one-way ANOVA (F2,135 = 4.271, p = 0.015; etasquared: 0.06); LSD post-hoc test revealed that the DTC [cube-root] of standing balance was greater in RR than either HCs and SP (p = 0.012—eta-squared = 0.12, and p = 0.045—eta-squared = 0.06, respectively), while any significant difference was found between SP and HCs (p = 0.583). Notably, SP group committed a slightly greater number of errors at Stroop test than RR group (p = 0.07).
3.3. Determinants of dual-task cost of balance The Spearman’s correlations (see also Table 2) revealed that postural balance in either single-task and dual-task condition was related with MS duration, EDSS score, walking speed, MSWS-12 and corrected SDMT score (p < 0.05). Fair relationships were also found between COP pathStroop and age (p = 0.005), and between DTC of standing balance and corrected SDMT (p = 0.021). The number of errors at Stroop test did not correlate neither with posturographic measures, nor with DTC or SDMT (p > 0.05).
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accounted for about 40% of the explained variability in this measure; the regression equation was: COP pathStroop [log10] = 2.551 + 0.091 (EDSS score) 0.005 (corrected SDMT score). The DTC of standing balance was associated with phenotype and corrected SDMT score; these two variables accounted for about 30% of the explained variability in this measure; the regression equation was: COP pathStroop [log10] = 5.908 1.472 (1 if SP, 0 if RR) 0.061 (corrected SDMT score). 4. Discussion
Fig. 1. Postural sway, expressed as mean centre of pressure (COP) path [log10] with relative 95% confidence intervals, for each group (relapsing-remitting multiple sclerosis, secondary-progressive multiple sclerosis and healthy controls) and condition (single-task: eyes opened, and dual-task: while performing the Stroop test).
In HC group a significant relationship was observed between COP pathEO and height (rho = 0.352, p = 0.018). Interestingly, we also found a significant relationship between DTC of standing balance and educational level (rho = 0.341, p = 0.019). Findings from multivariable linear regression analyses with outcome measures as dependent variables are shown in Table 3. Postural balance in single-task condition was associated with EDSS score; this variable accounted for about 37% of the explained variability in this measure; the regression equation was: COP pathEO [log10] = 2.396 + 0.076 (EDSS score). Postural balance in dual-task condition was associated with EDSS score and corrected SDMT score; these two variables Table 2 Non-parametric correlation coefficients, with their relative level of significance, in patients with MS (n = 92). COP pathEO
COP pathStroop
DTC
Age
rho p
0.194 0.063
0.292 0.005
0.134 0.202
Height
rho p
0.068 0.529
0.034 0.750
0.022 0.834
Weight
rho p
0.154 0.149
0.095 0.368
0.029 0.784
BMI
rho p
0.127 0.226
0.048 0.647
0.071 0.503
Educational level
rho p
0.201 0.054
0.192 0.067
0.040 0.706
Disease duration
rho p
0.291 0.005
0.391
